| Autor: |
Thijs J. Sluiter, Renée J. H. A. Tillie, Alwin de Jong, Jenny B. G. de Bruijn, Hendrika A. B. Peters, Remco van de Leijgraaf, Raghed Halawani, Michelle Westmaas, Lineke I. W. Starink, Paul H. A. Quax, Judith C. Sluimer, Margreet R. de Vries |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 13, Iss 3 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2047-9980 |
| DOI: |
10.1161/JAHA.123.033109 |
| Popis: |
Background Intraplaque angiogenesis occurs in response to atherosclerotic plaque hypoxia, which is driven mainly by highly metabolically active macrophages. Improving plaque oxygenation by increasing macrophage hypoxic signaling, thus stimulating intraplaque angiogenesis, could restore cellular function and neovessel maturation, and decrease plaque formation. Prolyl hydroxylases (PHDs) regulate cellular responses to hypoxia. We therefore aimed to elucidate the role of myeloid PHD2, the dominant PHD isoform, on intraplaque angiogenesis in a murine model for venous bypass grafting. Methods and Results Myeloid PHD2 conditional knockout (PHD2cko) and PHD2 wild type mice on an Ldlr−/− background underwent vein graft surgery (n=11–15/group) by interpositioning donor caval veins into the carotid artery of genotype‐matched mice. At postoperative day 28, vein grafts were harvested for morphometric and compositional analysis, and blood was collected for flow cytometry. Myeloid PHD2cko induced and improved intraplaque angiogenesis by improving neovessel maturation, which reduced intraplaque hemorrhage. Intima/media ratio was decreased in myeloid PHD2cko vein grafts. In addition, PHD2 deficiency prevented dissection of vein grafts and resulted in an increase in vessel wall collagen content. Moreover, the macrophage proinflammatory phenotype in the vein graft wall was attenuated in myeloid PHD2cko mice. In vitro cultured PHD2cko bone marrow–derived macrophages exhibited an increased proangiogenic phenotype compared with control. Conclusions Myeloid PHD2cko reduces vein graft disease and ameliorates vein graft lesion stability by improving intraplaque angiogenesis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Plný text